ObjectivesTo collect the methodology and original articles on the published cohort multiple randomized controlled trial (cmRCT), and evaluate the development and application of cmRCT.MethodsPubMed, EMbase, CNKI, WanFang Data and CBM databases were electronically searched to collect studies on cmRCT from inception to September 2019. Two reviewers independently screened literature, extracted data and assessed risk of bias of included studies, then qualitative analysis was conducted.ResultsA total of 21 studies were enrolled, including 5 original studies and 16 methodology studies. The design of cmRCT was proposed in year 2010 and continuous progress was observed, including aspect of informed consent and statistical analysis, etc. This design has been mainly utilized for chronic diseases (oncology etc.) in Europe; most of these ongoing studies were unpublished. However, to our knowledge, there were none published Chinese original studies or protocols using cmRCT design.ConclusionscmRCT design has been continuously developed and applied since its introduction. This design can be considered in Chinese studies based on Chinese large cohorts to provide more evidence for disease prevention and treatment.
Objective To investigate the effect of allogeneic chondrocytes-calcium alginate gel composite under the intervention of low intensive pulsed ultrasound (LIPUS) for repairing rabbit articular cartilage defects. Methods Bilateral knee articular cartilage were harvested from 8 2-week-old New Zealand white rabbits to separate the chondrocytes by mechanical-collagen type II enzyme digestion. The 3rd passage chondrocytes were diluted by 1.2% sodium alginate to 5 × 106 cells/mL, then mixed with CaCl2 solution to prepare chondrocytes-calcium alginate gel composite, which was treated with LIPUS for 3 days (F0: 1 MHz; PRF: 1 kHz; Amp: 60 mW/cm2; Cycle: 50; Time: 20 minutes). An articular cartilage defect of 3 mm in diameter and 3 mm in thickness was established in both knees of 18 New Zealand white rabbits (aged 28-35 weeks; weighing, 2.1-2.8 kg), and divided into 3 groups randomly, 6 rabbits in each group: LIPUS group, common group, and model group. Defect was repaired with LIPUS-intervention gel composite, non LIPUS-intervention gel composite in LIPUS group and common group, respectively; defect was not treated in the model group. The general condition of rabbits was observed after operation. The repair effect was evaluated by gross and histological observations, immunohistochemical staining, and Wakitani score at 8 and 12 weeks after operation. Results Defect was filled with hyaline chondroid tissue and white chondroid tissue in LIPUS and common groups, respectively. LIPUS group was better than common group in the surface smooth degree and the degree of integration with surrounding tissue. Defect was repaired slowly, and the new tissue had poor elasticity in model group. Histological observation and Wakitani score showed that LIPUS group had better repair than common group at 8 and 12 weeks after operation; the repair effect of the 2 groups was significantly better than that of model group (P lt; 0.05); and significant differences in repair effect were found between at 8 and 12 weeks in LIPUS and common groups (P lt; 0.05). The collagen type II positive expression area and absorbance (A) value of LIPUS and common groups were significantly higher than those of model group (P lt; 0.05) at 8 and 12 weeks after operation, and the expression of LIPUS group was superior to that of common group at 12 weeks (P lt; 0.05); and significant differences were found between at 8 and 12 weeks in LIPUS group (P lt; 0.05), but no significant difference between 2 time points in common and model groups (P gt; 0.05). Conclusion Allogeneic chondrocytes-calcium alginate gel composite can effectively repair articular cartilage defect. The effect of LIPUS optimized allogeneic chondrocytes-calcium alginate gel composite is better.
After the articular cartilage injury, the metabolic level is increased during the progressive degeneration, the chondrocytes secrete a variety of inflammatory factors, and the original cell phenotype is gradually changed. For a long time, a large number of researchers have done a lot of researches to promote anabolism of chondrocytes and to maintain the stability of chondrocyte phenotype. There are many molecular signaling pathways involved in the process of promoting cartilage repair. This review focuses on the key signaling molecules in articular cartilage repair, such as transforming growth factor-beta and bone morphogenetic protein, and reveals their roles in the process of cartilage injury and repair, so that researchers in related fields can understand the molecular mechanism of cartilage injury and repair widely and deeply. Based on this, they may find promising targets and biological methods for the treatment of cartilage injury.
As a kind of mechanical effector cells, chondrocytes can produce a variety of physical and chemical signals under the stimulation of multiaxial load in vivo, which affect their own growth, development and apoptosis. Therefore, simulating the mechanical environment in vivo has become a research hotspot in the culture of chondrocytes in vitro. Although a large number of reports have fully proved that different mechanical stimulation can regulate the metabolism of chondrocytes, the loading scheme has not been agreed. Starting from different mechanical forms, this review will explore the differences in the regulation of chondrocyte metabolism by different mechanical stimuli, so as to find an advantage scheme to promote the growth and proliferation of chondrocytes and to develop a more stable, effective and reliable experimental strategy.
Objective To analyze the prospective effect of pre-existing spinal stenosis of adjacent segment on the short-term effectiveness after lumbar fusion surgery. Methods A prospective comparative study was conducted to divide 183 patients with L4-S1 lumbar spinal stenosis who met the selection criteria between July 2015 and December 2017 into two groups according to the status of adjacent segment degeneration (ASD) judged by preoperative disc degeneration and spinal stenosis. There were 98 patients in group A (no degeneration of adjacent segments before operation) and 85 patients in group B (adjacent segments degenerated before operation). There was no significant difference in gender, American Society of Anesthesiologists (ASA) grade, body mass index (BMI), combined spondylolisthesis, and preoperative visual analogue scale (VAS) score of low back pain and leg pain, Japanese Orthopaedic Association (JOA) score, and Oswestry disability index (ODI) score between the two groups (P>0.05); the age of group A was significantly younger than that of group B (t=−3.560, P=0.000). The operation time, intraoperative blood loss, hospitalization stay, and perioperative complications were recorded and compared. The VAS score of low back pain and leg pain, JOA score, and ODI score at last follow-up were used to evaluate the effectiveness. The incidence of ASD after operation was compared between the two groups, and logistic regression was used to analyze the independent risk factors affecting the occurrence of ASD after operation. Results There was no significant difference in operation time, intraoperative blood loss, and hospitalization stay between the two groups (P>0.05). The incidence of perioperative complications in groups A and B was 13.3% and 20.0%, respectively, with no significant difference (χ2=1.506, P=0.220). Two groups of patients were followed up, the follow-up time of groups A and B was (24.9±8.8) months and (24.8±7.8) months, respectively, there was no significant difference (t=0.050, P=0.960). At last follow-up, no adjacent segment disease was found in either group. There was no significant difference in Pfirrmann grade between the two groups at last follow-up (P>0.05), and there was significant difference in Pfirrmann grade between the two groups before operation and at last follow-up (P<0.001). At last follow-up, 21 cases (21.4%) in group A and 53 cases (62.4%) in group B had ASD, with significant difference (χ2=31.652, P=0.000). The main cause of ASD was the severity of adjacent spinal canal stenosis. The clinical scores of the two groups at last follow-up were significantly improved when compared with those before operation (P<0.05). The JOA score of group A was significantly higher than that of group B at last follow-up (P<0.05). In group B, the VAS score of low back pain and ODI score in patients with ASD after operation at last follow-up were significantly higher than those in patients without ASD (P<0.05). logistic regression analysis showed that preoperative pre-existing degeneration and BMI were independent risk factors for ASD after operation (P<0.05). Conclusion Pre-existing mild spinal stenosis in adjacent segment can significantly affect the effectiveness, and can significantly increase the risk of ASD early after operation. The main pathological type of ASD was the severity of adjacent segment spinal stenosis. For preoperative assessment of pre-existing degeneration, we should evaluate the overall degeneration of the adjacent segment of the spinal canal, rather than simply evaluating the degeneration of the adjacent disc and facet joints.
Objective To prepare the silk fibroin microcarrier loaded with clematis total saponins (CTS) (CTS-silk fibroin microcarrier), and to investigate the effect of microcarrier combined with chondrocytes on promoting rabbit knee articular cartilage defects repair. Methods CTS-silk fibroin microcarrier was prepared by high voltage electrostatic combined with freeze drying method using the mixture of 5% silk fibroin solution, 10 mg/mL CTS solution, and glycerin. The samples were characterized by scanning electron microscope and the cumulative release amount of CTS was detected. Meanwhile, unloaded silk fibroin microcarrier was also prepared. Chondrocytes were isolated from knee cartilage of 4-week-old New Zealand rabbits and cultured. The 3rd generation of chondrocytes were co-cultured with the two microcarriers respectively for 7 days in microgravity environment. During this period, the adhesion of chondrocytes to microcarriers was observed by inverted phase contrast microscope and scanning electron microscope, and the proliferation activity of cells was detected by cell counting kit 8 (CCK-8), and compared with normal cells. Thirty 3-month-old New Zealand rabbits were selected to make bilateral knee cartilage defects models and randomly divided into 3 groups (n=20). Knee cartilage defects in group A were not treated, and in groups B and C were filled with the unloaded silk fibroin microcarrier-chondrocyte complexes and CTS-silk fibroin microcarrier-chondrocyte complexes, respectively. At 12 weeks after operation, the levels of matrix metalloproteinase 9 (MMP-9), MMP-13, and tissue inhibitor of MMP 1 (TIMP-1) in articular fluid were detected by ELISA. The cartilage defects were collected for gross observation and histological observation (HE staining and toluidine blue staining). Western blot was used to detect the expressions of collagen type Ⅱ and proteoglycan. The inflammatory of joint synovium was observed by histological staining and inducible nitric oxide synthase (iNOS) immunohistochemical staining. Results The CTS-silk fibroin microcarrier was spherical, with a diameter between 300 and 500 μm, a porous surface, and a porosity of 35.63%±3.51%. CTS could be released slowly in microcarrier for a long time. Under microgravity, the chondrocytes attached to the surface of the two microcarriers increased gradually with the extension of culture time, and the proliferation activity of chondrocytes at 24 hours after co-culture was significantly higher than that of normal chondrocytes (P<0.05). There was no significant difference in proliferation activity of chondrocytes between the two microcarriers (P>0.05). In vivo experiment in animals showed that the levels of MMP-9 and MMP-13 in group C were significantly lower than those in groups A and B (P<0.05), and the level of TIMP-1 in group C was significantly higher (P<0.05). Compared with group A, the cartilage defects in groups B and C were filled with repaired tissue, and the repaired surface of group C was more complete and better combined with the surrounding cartilage. Histological observation and Western blot analysis showed that the International Cartilage Repair Scoring (ICRS) and the relative expression levels of collagen type Ⅱ and proteoglycan in groups B and C were significantly better than those in group A, and group C was significantly better than group B (P<0.05). The histological observation showed that the infiltration of synovial inflammatory cells and hyperplasia of small vessels significantly reduced in group C compared with groups A and B. iNOS immunohistochemical staining showed that the expression of iNOS in group C was significantly lower than that in groups A and B (P<0.05).Conclusion CTS-silk fibroin microcarrier has good CTS sustained release effect and biocompatibility, and can promote the repair of rabbit cartilage defect by carrying chondrocyte proliferation in microgravity environment.